The T cell response to rapidly evolving HIV antigens

描述（由申请人提供）：抗病毒CD8+ T细胞在HIV复制的初始控制中发挥重要作用，可能有助于延缓HIV感染者的艾滋病发病。为了了解抗病毒CD8+ T细胞在免疫保护中的作用，有必要全面表征CD8+ T细胞在hiv感染患者中的特异性。实现这一目标的一个主要障碍是来自不同个体的HIV临床分离株之间的高度遗传变异性。目前大多数筛选T细胞特异性的技术依赖于参考菌株抗原或代表共识序列的合成肽。这些方法可能低估了由于检测抗原和自体病毒之间的遗传差异而引起的T细胞反应。该建议描述了一种方法，基于转染合成mRNA的抗原提呈细胞，用于有效筛选患者CDS+ T细胞对自身HIV抗原的反应。这种方法将用于比较慢性HIV感染中T细胞对自体抗原和共识抗原的反应。

DESCRIPTION (provided by applicant): Antiviral CD8+ T cells play an important role in initial control of HIV replication and presumably help delay the onset of AIDS in HIV infected individuals. In order to understand the role of antiviral CD8+ T cells in immune protection, it will be necessary to comprehensively characterize the specificities CD8+ T cells in HIV-infected patients. A major obstacle to this goal is the high degree of genetic variability among HIV clinical isolates from different individuals. Most current techniques to screen T cell specificities rely on reference strain antigens or synthetic peptides representing a consensus sequence. These methods may underestimate T cell response due to genetic divergence between the assay antigen and autologous virus. This proposal describes an approach, based on transfection of antigen presenting cells with synthetic mRNA, for efficient screening of patient CDS+ T cell responses to autologous HIV antigens. This method will be used to compare the T cell responses to autologous and consensus antigens in chronic HIV infection.